Despite the failure of previous malaria eradication program, the world is currently working to eliminate and ultimately eradicate malaria. One of the most important tools to achieve this goal is antimalarial drugs. These drugs, starting from the oldest quinine and progressing to chloroquine, sulfadoxine-pyrimethamine, mefloquine and the currently utilized artemisinin based combination therapy, have played significant role in the recorded successes of malaria control and elimination. However, the recent emergence of parasites with decreased susceptibility to artemisinin and related malaria treatment failure in Southeast Asian countries appeared as a big threat against the success. In 2014, mutations in the propeller domain of the kelch protein (K13), associated with phenotypic markers of artemisinin resistance, were identified as candidate molecular markers of resistance. Several cellular stress response pathways such as K13-dependent alterations in phosphatidylinositol-3-kinase (PfPI3K) are being forwarded as potential molecular resistance mechanisms. Consequently, malaria community is working to counteract the problem through application of several strategies ranging from surveillance of resistant strains to the development of new drugs. Additionally, vaccine development and Mass Drug Administration (MDA) are other alternatives under scientific scrutiny. This review will discuss and examine in detail about these and other related issues.

Key words: Artemisinin resistance, kelch 13, phenotypic markers, phosphatidylinositol-3-kinase, unfolded protein response.